Biodegradable polymers have shown wide utility in a variety of biomedical applications ranging from sutures, scaffolds for the growth of cells, and polymeric depots that provided sustained release of therapeutic agents [1-6]. Optimal use of these materials requires their molecular and macromolecular properties be tailored to the specific application for which the material is to be used [3, 7-9]. For instance, polymeric particles loaded with drugs that are targeted to the endosomal compartments of cells should ideally be stable at physiological pH in the bloodstream, but readily break down at a lower pH to release their drug cargo in the endosome where the pH is approximately 4 to 5 [10-13].
Biodegradable polymers are attractive in drug delivery applications because polymeric particles injected in vivo can accumulate in several organs including the liver, spleen, lungs and heart and often result in toxic side effects if they do not break apart into smaller, easily excretable side products [14, 15]. The degradation of these polymers is also one of the mechanisms by which controlled release of drugs and other therapeutics is achieved. Most synthetic polymers in biomedical applications are polyesters, polyamides, polyanhydrides, or polymers featuring two or more of the ester, amide, and anhydride groups. Ideally, such polymers degrade to short polymers or small molecules at reasonable times without the use of enzymes [16-18]. Thus, these polymers can be excreted from the body before toxic side-effects occur.
Moreover, microparticles containing a drug should be stable in the bloodstream where the pH is 7.4; however, when they are endocytosed into a cell they should break down rapidly in the endosome/lysosome where the pH is approximately 4 to 5. Another challenge in the field of drug delivery via synthetic polymers is the need to fabricate “smart” delivery vehicles that target selected cells. Targeting of cells is most commonly done by placing ligands on the surface of the microparticles that are recognized by selected cells. The most common biodegradable polymer used in drug delivery applications is poly(lactic-co-glycolic acid), but this polymer lacks reactive surface functional groups that can be functionalized to expose ligands to direct attachment to cells.
It can be very challenging to design a polymer with a new functional group along its backbone that renders it stable at physiological pH but also allows it to be degraded at reasonable time scales in the body without toxic side effects. The introduction of a new functional group that can be used to synthesize biopolymers has the potential to open up new applications in this field and will allow more complex, potentially “smart” drug delivery vehicles to be synthesized [7, 11, 17].
Sulfenamides are an understudied inorganic functional group with the general formula of RS—NR′ that are used as protecting groups for amines (typically as (Ph3C)S—NR′) [44], vulcanizing agents in the rubber industry [45], in the activation of C—H bonds [46], as ligands on metals to promote oxygen atom transfer [47], as intermediates in the synthesis of sulfenamides [48], as oxidants for alcohols [49], and as ligands in the synthesis of inorganic coordination compounds.[50, 51]. Although sulfenamides are well studied in small molecule synthesis, no examples of polysulfenamides are known.